Biomarkers for Prognosis of Glioblastoma (GBM)
The purpose of this study is:
- To learn if (MMP-2, MMP-9 and NGAL) which are substances found in blood and urine associated with tumors, can be used as tumor markers in the management and treatment of glioblastoma.
- To study the relationship between MMP-2, MMP-9 and NGAL with quality of life and disease symptoms.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||MMP-2, MMP-9 and NGAL as Biomarkers for Glioblastoma (GBM) Biomarkers for the Prognosis of Glioblastoma|
- To estimate the amount of MMP-2, MMP-9 and MMP-9/NGAL using immunohistochemistry in tumor tissue and non-tumor (epilepsy) patients. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]The mean MMP-2, MMP-9 and NGAL will be estimated using 95% confidence intervals, for the GBM and control groups. In the event that the data are not normally distributed and a suitable transformation is not evident, the median and a 95% confidence for a median will be used.
- To provide preliminary evidence that MMP-2, MMP-9 and MMP-9/NGAL in tissue corresponds with their presence in the urine and blood in patients undergoing surgery for epilepsy (Aim 1a) and in patients with grade IV glioma (Aim 1b). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]For each outcome (MMP-2, MMP-9 and MMP-9/NGAL), Pearson's correlation coefficient will be used to examine the association between 1) tissue and urine and 2) tissue and blood. Spearman's correlation will be used in the event that the data are not normally distributed and a suitable transformation is not evident. Due to the anticipated interaction of group with presence of these biomarkers, these analyses will be conducted separately for epilepsy control patients and GBM patients.
- To examine the association between the change in urine and serum MMP-2, MMP-9 and MMP-9/NGAL levels with changes in tumor burden. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]For each outcome (MMP-2, MMP-9 and MMP-9/NGAL), Pearson's correlation coefficient will be used to examine the association between 1) tissue and urine and 2) tissue and blood. Spearman's correlation will be used in the event that the data are not normally distributed and a suitable transformation is not evident. Due to the anticipated interaction of group with presence of these biomarkers, these analyses will be conducted separately for epilepsy control patients and GBM patients
- To descriptively examine quality of life (QOL) measurements and symptoms measurements. [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]QOL and symptoms measurements will be descriptively summarized using means, medians, standard deviations, and ranges (for continuous data) and frequencies and percentages (for categorical data), along with corresponding 95% confidence intervals.
- To estimate the association of post-operative biomarker levels with time to progression (TTP) and overall survival (OS). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]As an exploratory analysis, the association of MMP-2, MMP-9 and MMP-9/NGAL at 24h and 48h post-op will be summarized examined using a Cox-proportional hazards regression model
Biospecimen Retention: Samples Without DNA
Whole Blood, Urine, and Tissue.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Matrix metalloproteinases (MMP) -2 and -9 belong to a multigene family of degradative enzymes implicated in the neoangiogenesis required for tumor growth. In the central nervous system (CNS), MMP-2, MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL) are overexpressed in orthotopic models and also in human brain tumor specimens. Furthermore, serum and urinary levels of these markers have been shown to correlate with the presence and status of brain tumors in all types of primary brain tumors. A major challenge in the treatment of primary brain tumors is the dependence on magnetic resonance imaging (MRI) to differentiate disease progression from treatment-related change. This is particularly challenging in glioblastomas (GBM) where multimodality therapy with radiation and chemotherapy is commonly used and can lead to pseudoprogression and treatment-related tissue necrosis, both of which can masquerade as true tumor progression. Often we are faced with the decision to treat based on imaging findings alone or to recommend that patients have another invasive surgery. We hypothesize that MMP-2, MMP-9 and NGAL will: 1) be detected on tumor tissue by immunohistochemistry and not on non-tumor (epilepsy) brain tissue, 2) parallel the course of disease in the urine and/or serum of patients and 3) remain unchanged in the event of pseudoprogression and treatment related imaging changes. Quality of life, patient symptoms, and cognitive function are vitally important in patients with GBM. Quality of life and selected symptoms will also be assessed and correlated with serum and urine biomarkers. We hope to confirm the utility of MMP-2, MMP-9 and NGAL in the management of GBM.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01493219
|Contact: Nicole Shonka, MDemail@example.com|
|Contact: Alice Kueh, MSfirstname.lastname@example.org|
|United States, Nebraska|
|University of Nebraska Medical Center||Recruiting|
|Omaha, Nebraska, United States, 68198|
|Contact: Alice Kueh, MS 402-559-8511 email@example.com|
|Principal Investigator: Nicole Shonka, MS|
|Principal Investigator:||Nicole Shonka, MD||UNMC|